Nat Commun
August 2025
Despite the efficacy of chimeric antigen receptor (CAR)-T cells in selected hematological malignancies, further improvement on CAR-T designs is still desirable. We hypothesize that modifying the CAR structure to enhance immunological synapse (IS) stabilization and CAR target-binding may be a feasible strategy. Here we show that the membrane protein, CD99, is critical for IS formation in T cells by mediating actin-microtubule interaction.
View Article and Find Full Text PDFObjectives: Patients initially diagnosed with idiopathic late-onset cerebellar ataxia (ILOCA) may develop multiple system atrophy cerebellar type (MSA-C). However, data on conversion time, associated clinical factors, and the role of the neurofilament light chain (NFL) in this process remain limited. This study aims to investigate the conversion from ILOCA to MSA-C and examine the associated factors and the predictive value of NFL.
View Article and Find Full Text PDFTransl Vis Sci Technol
August 2025
Purpose: This study aims to understand the differences in cellular and molecular patterns between the Main and Accessory (Acc) regions of pterygium tissue, with a focus on inflammation and mitochondrial energy metabolism.
Methods: We collected bulk RNA sequencing (RNA-seq) data from six pterygium patients and single-cell RNA-seq data from two pterygium patients. Subsequently, we investigated pathway enrichment, pathway correlation, differential gene expression, protein-protein interactions, and cell-cell communication in pterygium.
Mutations in the COL2A1 gene, encoding procollagen-II, cause various chondrodysplasias, including precocious osteoarthritis with mild spondyloepiphyseal dysplasia engendered by the p.Arg719Cys substitution. The molecular mechanisms underlying these disorders remain incompletely understood, largely owing to the absence of models faithfully recapitulating the human disease.
View Article and Find Full Text PDFMDGA1 reportedly suppresses GABAergic synaptic inhibition, but it is unclear whether and how MDGA1 dysfunction causes neurodevelopmental disorders. Here, we describe two patients with autism spectrum disorders (ASDs) each carrying pairs of novel missense mutations in , Val116Met/Ala688Val and Tyr635Cys/Glu756Gln. The Tyr635Cys/Glu756Gln substitution (but not the Val116Met/Ala688V substitution) disrupts the triangular extracellular structure of MDGA1 and renders it unable to impact GABAergic synapses in both cultured hippocampal neurons and hippocampal CA1 pyramidal neurons.
View Article and Find Full Text PDFFront Immunol
June 2025
Messenger RNA (mRNA) vaccines represent a critical avenue for coronavirus disease 2019 (COVID-19) prevention. We developed a COVID-19 mRNA vaccine encoding a codon-optimized full-length ancestral spike (S) protein with a signal peptide, which employs our novel patented co-transcriptional 5'-capping reagent, SmartCap. From the screening capping library of SmartCap, an SC101 cap was selected to derive a novel mRNA vaccine, STP2104.
View Article and Find Full Text PDFHeterologous vaccination strategies have shown superior efficacy over homologous regimens in clinical studies, but the underlying immunological mechanisms remain incompletely understood. Using a mouse model, we investigated the immune responses induced by heterologous prime-boost vaccination with adenoviral and mRNA vaccines. Heterologous vaccination (adenoviral prime, mRNA boost) elicited higher neutralizing antibody titers and stronger CD8 T cell responses against Delta and Omicron-BA.
View Article and Find Full Text PDFNat Commun
May 2025
Genome-wide association studies (GWAS) on Alzheimer's disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (APCDD1) associated with AD.
View Article and Find Full Text PDFAlthough growing evidence suggests that cholinergic basal forebrain degeneration is linked to cognitive impairment and axial motor symptoms in Lewy body disorders (LBDs), the cholinergic contribution to their prodromal phase remains largely unknown. Herein, we aimed to address three important yet unresolved questions focusing on prodromal LBDs: (1) to examine whether and where basal forebrain degeneration begins; (2) to determine how such alterations are related to other brain morphometric changes and monoaminergic deficits; and (3) to investigate the extent to which basal forebrain atrophy contributes to the clinical picture. We included 93 patients with polysomnography-confirmed isolated REM sleep behavior disorder (iRBD), 33 with de novo Parkinson's disease (PD) with a premorbid history of RBD (dnPDRBD), and 36 healthy controls.
View Article and Find Full Text PDFFeline pyothorax or thoracic empyema is a condition characterized by the accumulation of purulent exudate within the thoracic cavity due to infection [...
View Article and Find Full Text PDFCardiac tissue lacks regenerative capacity, making heart transplantation the primary treatment for end-stage heart failure. Engineered cardiac tissues developed through three-dimensional bioprinting (3DBP) offer a promising alternative. However, reproducing the native structure, cellular diversity, and functionality of cardiac tissue requires advanced cardiac bioinks.
View Article and Find Full Text PDFDirecting regioselectivity and stereoselectivity in allene reactions has long been a significant challenge due to the multiple reactive pathways available. In this study, we report the development of a Ni-catalyzed regio- and stereoselective 2,3-hydrosilylation of 1,1-disubstituted allenes. Stereoselectivity was precisely controlled through the strategic modulation of ligand-induced steric effects and non-covalent interactions.
View Article and Find Full Text PDFAlzheimers Dement
February 2025
Introduction: Isolated REM sleep behavior disorder (iRBD) is a strong prodromal marker of Lewy body diseases (LBDs) - Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Cholinergic loss is linked to cognitive decline in these conditions, but its trajectory remains unclear.
Methods: In a cohort of 92 iRBD participants with baseline MRI, cholinergic basal forebrain (cBF) volume was measured, with longitudinal changes analyzed in 49 with follow-up scans.
J Clin Invest
April 2025
RAS/MAPK pathway mutations often induce RASopathies with overlapping features, such as craniofacial dysmorphology, cardiovascular defects, dermatologic abnormalities, and intellectual disabilities. Although B-Raf proto-oncogene (BRAF) mutations are associated with cardio-facio-cutaneous (CFC) syndrome and Noonan syndrome, it remains unclear how these mutations impair cognition. Here, we investigated the underlying neural mechanisms using several mouse models harboring a gain-of-function BRAF mutation (K499E) discovered in RASopathy patients.
View Article and Find Full Text PDFThe SARS-CoV-2 virus is continuously evolving, such that JN.1 and its subvariants, including KP.2, KP.
View Article and Find Full Text PDFParkinsonism Relat Disord
March 2025
Background: Previous studies have used machine learning to identify clinically relevant atrophic regions in progressive supranuclear palsy (PSP). This study applied Elastic Net (EN) in PSP to uncover key atrophic patterns, offering a novel approach to understanding its pathology.
Methods: This study included baseline data from 74 patients with PSP enrolled in the Study of Comprehensive ANd multimodal marker-based cohort of PSP (SCAN-PSP, NCT05579301) in Seoul between January 2022 and August 2023.
Parkinsonism Relat Disord
March 2025
Introduction: In isolated REM sleep behavior disorder (iRBD), the evidence of cognitive impairment and co-existing amyloid pathology suggests that mild behavioral impairment (MBI) may be associated with disease progression. In this study, we investigated MBI and its association with cognitive function, brain amyloid load and glucose metabolism in iRBD patients to evaluate the utility of MBI as a predictive marker of disease progression.
Methods: Patients with iRBD underwent a neuropsychological evaluation, F-florbetaben (FBB) PET, and F-fluorodeoxyglucose (FDG) PET.
J Clin Med
January 2025
: Sleep and mental health are crucial to elite youth athletes, who face combined pressures of training, competition, school, and social commitments. We examined the association between sleep and depression in elite youth athletes. : We analyzed data of 248 Korean world-class youth athletes (aged 13-19 years).
View Article and Find Full Text PDFClin Park Relat Disord
December 2024
Background: There remains a significant gap in systematic research on healthcare utilization behaviors and the influencing factors for patients with Parkinson's disease (PD), particularly those in late stages.
Methods: PD patients in late stage (Hoehn and Yahr (HY) stages 4 and 5) and their caregivers from Seoul National University Hospital Movement Disorders Clinic participated. A total of 103 respondents completed a questionnaire covering medical utilization behaviors, perceptions of face-to-face and telemedicine consultations, and additional medical service needs.
J Neural Transm (Vienna)
May 2025
To investigate the clinical impact of mild behavioral impairment (MBI) in a predefined cohort with Lewy body disease (LBD) continuum. Eighty-four patients in the LBD continuum participated in this study, including 35 patients with video-polysomnography-confirmed idiopathic REM sleep behavior disorder (iRBD) and 49 clinically established LBD. Evaluations included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), neuropsychological tests, and MBI Checklist (MBI-C).
View Article and Find Full Text PDFRecent cohort studies suggest a potential association between atopic dermatitis and dementia, though the evidence remains conflicting. This study aims to elucidate the association between atopic dermatitis and dementia employing systematic review, meta-analysis, and Mendelian randomization (MR). A comprehensive search was performed to select eligible cohort studies using Medline, Embase, Scopus, ScienceDirect, and the Web of Science database.
View Article and Find Full Text PDFObjective: This study aims to objectively evaluate turning gait parameters in Parkinson's disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance.
Methods: We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations.
Nat Commun
November 2024